1,721,043 research outputs found

    Understanding collagen interactions and their targeted regulation by novel drugs

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    Introduction: Among protein and fibers in the extracellular matrix (ECM), collagen is the most copious and widely employed in cosmetic, food, pharmaceutical, and biomedical industries due to its extensive biocompatible and versatile properties. In the last years, the knowledge about functions of collagens increased and expanded dramatically. Once considered only crucial for the ECM scaffolding and mechanotransduction, additional functional roles have now been ascribed to the collagen superfamily which are defined by other recently discovered domains, supramolecular assembly and receptors. Areas covered: Given the importance of each step in the collagen biosynthesis, folding and signaling, medicinal chemists have explored small molecules, peptides, and monoclonal antibodies to modulate enzymes, receptors and interactions with the physiological ligands of collagen. These compounds were also explored toward diseases and pathological conditions. The authors discuss this providing their expert perspectives on the subject area. Expert opinion: Understanding collagen protein properties and its interactome is beneficial for therapeutic drug design. Nevertheless, compounds targeting collagen-based interactome suffered from the presence of different isoforms for each target and the lack of specific 3D crystal structures able to guide properly drug design

    Nrf2-mediated cytoprotective effect of four different hyaluronic acids by molecular weight in human tenocytes

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    Non-traumatic rotator cuff tears (RCTs) are a frequent and potentially disabling injury. There is growing evidence that hyaluronic acid (HA) is effective for pain relief and to counteract inflammation in RCTs, however, its effective role in tendinopathies remains poorly studied. This study aims to disclose a possible molecular mechanism underlying the cytoprotective effects of four different HA preparations (Artrosulfur HA®, Synolis VA®, Hyalgan® and Hyalubrix®) under H2O2-induced oxidative stress. Expression-levels of Lactate dehydrogenase (LDH) released were quantified in cell supernatants, CD44 expression levels were analysed by fluorescence microscopy, the mitochondrial membrane depolarisation (TMRE assay) was measured by flow cytometry and the role of the transcription factor Nrf2 was investigated as a potential therapeutic target for RCT treatment. The modulation of extracellular matrix- (ECM) related protein expression (Integrin β1, pro-collagen 1A2 and collagen 1A1) and autophagy occurrence (Erk 1/2 and phosphoErk 1/2 and LC3B), were all investigated by Western Blot. Results demonstrate that Artrosulfur HA, Hyalubrix and Hyalgan improve cell escape from H2O2-induced oxidative stress, decreasing cytotoxicity, reducing Nrf2 expression and enhancing catalase recovery. This study lays the grounds for further investigations insight novel pharmaceutical strategies targeting key effectors involved in the molecular cascade triggered by HA

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Modulation of NRF2: Biological Dualism in Cancer, Targets and Possible Therapeutic Applications

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    Significance: The nuclear factor erythroid 2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) system is a master regulator of redox homeostasis and cell adaptation to a variety of exogenous and endogenous stressors. Accumulating evidence from the last decade indicates that the impairment of the redox balance leads to oxidative stress (OS), a common alteration occurring in many human acute and chronic inflammatory diseases, such as cancer, diabetes, neurodegeneration, and metabolic disorders, and aging. Recent Advances: Being located at the intersection of crucial signaling pathways, NRF2 can influence several cellular functions, which extend beyond the maintenance of the redox balance and include cellular metabolism, proteostasis, mitochondrial function and inflammation. For this reason, there is a growing interest in the pharmacologic manipulation of NRF2 for therapeutic purposes, which requires the accurate knowledge of the cell context and the specific time frame both of NRF2 activation and inhibition. This appears to be an important prerequisite and reflects the extreme complexity of the NRF2 signaling, characterized by an intrinsic dualism that mediates beneficial or detrimental effects even in the same biological process. Critical Issues: Of crucial importance will be to understand whether the NRF2 activity modulation might be exploited to exert beneficial outcomes in patients suffering from pathological conditions, in which the OS and the deregulation of inflammatory processes play a crucial role. Future Directions: In this review, we discuss the dual involvement of NRF2 in aging, neurodegeneration, metabolic diseases, long-COVID-19, and carcinogenesis and we present an overview of the most recent therapeutic modulators of NRF2, particularly emphasizing on those selected for clinical trials

    Determination of trace elements by INAA in urban air particulate matter and transplanted lichens

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    Lichens as biomonitors and neutron activation analysis as analytical technique have been employed to evaluate the trace element atmospheric pollution in the metropolitan area of the city of Pavia (Northern Italy). Transplanted lichens (Parmelia sulcata and Usnea gr. hirta) and air particulate matter have been monthly collected and analyzed during the winter 20012002. INAA and ET-AAS have been used for the determination of 28 elements in air particulate matter and 25 elements in lichens. Trace metals concentrations as well as the corresponding enrichment factors were evaluated and compared
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